Back to results

Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation

Primary Purpose

Hypercholesterolemia

Status

Completed

Phase

Phase 4

Locations

Israel

Study Type

Interventional

Intervention

Simvastatin

Ezetimibe

About this trial

This is an interventional treatment trial for Hypercholesterolemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Hypercholesterolemic patients on stable simvastatin dose for at least one month.
Age ≥18 years on stable AHA step 1 diet.
Patients without CHD or with one risk factors ; LDL > 130 mg/dL and for Patients with CHD or CHD risk equivalent(clinical manifestations of non-coronary forms of atherosclerotic disease) or with 2 risk f actors (cigarette smoking, hypertension (BP ≥140/90 mm Hg or on antihypertensive medication), low HDL cholesterol (<40 mg/dL), family history of premature CHD;LDL>100 mg/dL
Patients 'on at least simvastatin treatment of 20 mg per day.
CPK, ALT and AST < 1.5 X upper limit of normal at baseline.

Exclusion Criteria:

Women currently receiving cyclical hormones.
Treatment with psyllium, other fiber based laxatives, phytosterol margarines, or other OTCs that affect serum lipids, unless treated with a stable regimen for > 6 weeks and the patient agrees to continue this regimen for the duration of the trial.
Oral corticosteroids unless used as replacement therapy for pituitary/adrenal disease and a stable regimen for at least 6 weeks.
Lipid lowering agents including fish oils and QUESTRAN taken within 6 weeks.
Active coronary heart disease: unstable angina, acute myocardial infarction, CABG or PTCA within the last 3 months.
Women with childbearing potential unless on safe contraception.
Psychiatric disease with defect in judgement.
Severe renal or hepatic disease.
Uncontrolled hypo- or hyperthyroidism.
Contraindication for ezetimibe or simvastatin treatment. The patients will continue on their treatment with simvastatin for 6 weeks, and then the patients will be treated by the same dose of simvastatin combined with ezetimibe 10 mg/day for other 6 weeks.

Sites / Locations

Internal Medicine Department A ,Ziv Goverment Hospital

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

NCT ID

NCT00466401

First Posted

April 25, 2007

Last Updated

February 19, 2013

Sponsor

Ziv Hospital

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT00466401

Brief Title

Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation

Official Title

Phase 4 Study on Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation In Hypercholesterolemic Patients on Simvastatin

Study Type

Interventional

2. Study Status

Record Verification Date

February 2013

Overall Recruitment Status

Completed

Study Start Date

February 2005 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

August 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Ziv Hospital

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

5. Study Description

Brief Summary

The aim of our study is to Estimate the reduction of LDL by ezetimibe in hypercholesterolemic patients on simvastatin.Investigate the effect of LDL lowering by ezetimibe on platelet activity and LDL tendency to peroxidation in hypercholesterolemic patients on simvastatin therapy The hypothesis is that: LDL lowering by ezetimibe on-top of simvastatin in patients on fixed dose of simvastatin can reduce platelet aggregation, due to the potential decreasing of cholesterol content in the platelet membranes. LDL lowering by ezetimibe can lower LDL tendency to peroxidation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (false)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Simvastatin

Intervention Type

Drug

Intervention Name(s)

Ezetimibe

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Hypercholesterolemic patients on stable simvastatin dose for at least one month. Age ≥18 years on stable AHA step 1 diet. Patients without CHD or with one risk factors ; LDL > 130 mg/dL and for Patients with CHD or CHD risk equivalent(clinical manifestations of non-coronary forms of atherosclerotic disease) or with 2 risk f actors (cigarette smoking, hypertension (BP ≥140/90 mm Hg or on antihypertensive medication), low HDL cholesterol (<40 mg/dL), family history of premature CHD;LDL>100 mg/dL Patients 'on at least simvastatin treatment of 20 mg per day. CPK, ALT and AST < 1.5 X upper limit of normal at baseline. Exclusion Criteria: Women currently receiving cyclical hormones. Treatment with psyllium, other fiber based laxatives, phytosterol margarines, or other OTCs that affect serum lipids, unless treated with a stable regimen for > 6 weeks and the patient agrees to continue this regimen for the duration of the trial. Oral corticosteroids unless used as replacement therapy for pituitary/adrenal disease and a stable regimen for at least 6 weeks. Lipid lowering agents including fish oils and QUESTRAN taken within 6 weeks. Active coronary heart disease: unstable angina, acute myocardial infarction, CABG or PTCA within the last 3 months. Women with childbearing potential unless on safe contraception. Psychiatric disease with defect in judgement. Severe renal or hepatic disease. Uncontrolled hypo- or hyperthyroidism. Contraindication for ezetimibe or simvastatin treatment. The patients will continue on their treatment with simvastatin for 6 weeks, and then the patients will be treated by the same dose of simvastatin combined with ezetimibe 10 mg/day for other 6 weeks.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Osamah Hussein, MD

Organizational Affiliation

Ziv Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Internal Medicine Department A ,Ziv Goverment Hospital

City

Safed

ZIP/Postal Code

13100

Country

Israel

12. IPD Sharing Statement

Citations:

PubMed Identifier

11558859

Citation

Bays HE, Moore PB, Drehobl MA, Rosenblatt S, Toth PD, Dujovne CA, Knopp RH, Lipka LJ, Lebeaut AP, Yang B, Mellars LE, Cuffie-Jackson C, Veltri EP; Ezetimibe Study Group. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clin Ther. 2001 Aug;23(8):1209-30. doi: 10.1016/s0149-2918(01)80102-8. Erratum In: Clin Ther 2001 Sep;23(9):1601.

Results Reference

background

PubMed Identifier

12505224

Citation

Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP, Suresh R, Sun S, Veltri EP. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol. 2002 Dec 18;40(12):2125-34. doi: 10.1016/s0735-1097(02)02610-4.

Results Reference

background

PubMed Identifier

11375333

Citation

van Heek M, Austin TM, Farley C, Cook JA, Tetzloff GG, Davis HR. Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters. Diabetes. 2001 Jun;50(6):1330-5. doi: 10.2337/diabetes.50.6.1330.

Results Reference

background

PubMed Identifier

14675576

Citation

Sager PT, Melani L, Lipka L, Strony J, Yang B, Suresh R, Veltri E; Ezetimibe Study Group. Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C-reactive protein. Am J Cardiol. 2003 Dec 15;92(12):1414-8. doi: 10.1016/j.amjcard.2003.08.048.

Results Reference

background

PubMed Identifier

11742881

Citation

Davis HR Jr, Compton DS, Hoos L, Tetzloff G. Ezetimibe, a potent cholesterol absorption inhibitor, inhibits the development of atherosclerosis in ApoE knockout mice. Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):2032-8. doi: 10.1161/hq1201.100260.

Results Reference

background

PubMed Identifier

1861629

Citation

Lavy A, Brook GJ, Dankner G, Ben Amotz A, Aviram M. Enhanced in vitro oxidation of plasma lipoproteins derived from hypercholesterolemic patients. Metabolism. 1991 Aug;40(8):794-9. doi: 10.1016/0026-0495(91)90005-h.

Results Reference

background

PubMed Identifier

11476969

Citation

Hussein O, Frydman G, Frim H, Aviram M. Reduced susceptibility of low density lipoprotein to lipid peroxidation after cholestyramine treatment in heterozygous familial hypercholesterolemic children. Pathophysiology. 2001 Aug;8(1):21-28. doi: 10.1016/s0928-4680(01)00061-x.

Results Reference

background

PubMed Identifier

8380241

Citation

Surya II, Akkerman JW. The influence of lipoproteins on blood platelets. Am Heart J. 1993 Jan;125(1):272-5. doi: 10.1016/0002-8703(93)90096-r. No abstract available.

Results Reference

background

PubMed Identifier

2730708

Citation

Ardlie NG, Selley ML, Simons LA. Platelet activation by oxidatively modified low density lipoproteins. Atherosclerosis. 1989 Apr;76(2-3):117-24. doi: 10.1016/0021-9150(89)90094-4.

Results Reference

background

PubMed Identifier

9241100

Citation

Osamah H, Mira R, Sorina S, Shlomo K, Michael A. Reduced platelet aggregation after fluvastatin therapy is associated with altered platelet lipid composition and drug binding to the platelets. Br J Clin Pharmacol. 1997 Jul;44(1):77-83. doi: 10.1046/j.1365-2125.1997.00625.x.

Results Reference

background

PubMed Identifier

6626183

Citation

Aviram M. Plasma lipoprotein separation by discontinuous density gradient ultracentrifugation in hyperlipoproteinemic patients. Biochem Med. 1983 Aug;30(1):111-8. doi: 10.1016/0006-2944(83)90013-3.

Results Reference

background

PubMed Identifier

12713767

Citation

Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, LeBeaut AP, Suresh R, Yang B, Veltri EP; Ezetimibe Study Group. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J. 2003 Apr;24(8):729-41. doi: 10.1016/s0195-668x(02)00807-2.

Results Reference

background

Learn more about this trial

Effect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation

We'll reach out to this number within 24 hrs